Parathyroid Hormone Gene and Genes Involved in the Maintenance of Vitamin D Levels Association with Mandibular Retrognathism

Abstract

In this study we evaluated whether single nucleotide polymorphisms (SNPs) in the genes encoding PTH, VDR, CYP24A1, and CYP27B1 were associated with mandibular retrognathism (MR). Samples from biologically-unrelated Brazilian patients receiving orthodontic treatment were included in this study. Pre-orthodontic lateral cephalograms were used to determine the phenotype. Patients with a retrognathic mandible were selected as cases and those with an orthognathic mandible were selected as controls. Genomic DNA was used for genotyping analysis of SNPs in PTH (rs694, rs6256, and rs307247), VDR (rs7975232), CYP24A1 (rs464653), and CYP27B1 (rs927650). Chi-squared or Fisher's tests were used to compare genotype and allele distribution among groups. Haplotype analysis was performed for the SNPs in PTH. The established alpha was p < 0.05. Multifactor dimensionality reduction (MDR) was used to identify SNP-SNP interactions. A total of 48 (22 males and 26 females) MR and 43 (17 males and 26 females) controls were included. The linear mandibular and the angular measurements were statistically different between MR and controls (p < 0.05). In the genotype and allele distribution analysis, the SNPs rs694, rs307247, and rs464653 were associated with MR (p < 0.05). MDR analyses predicted the best interaction model for MR was rs694-rs927650, followed by rs307247-rs464653-rs927650. Some haplotypes in the PTH gene presented statistical significance. Our results suggest that SNPs in PTH, VDR, CYP24A1, and CYP27B1 genes are associated with the presence of mandibular retrognathism.

Keywords: gene; mandible; polymorphism; retrognathism.

Figure 1

Cephalometric tracings. (A) Exemplification of retrognathism (SNB > 78°). (B) Exemplification of orthognathic mandible (SNB ranging from 78° to 82°).

Figure 2

Flow chart of patient selection.

Figure 3

Interaction analysis for the studied SNPs by MDR. (A) Interaction dendrogram. Dendrogram shows keys connecting the SNPs. Strongly interacting SNPs are connected by keys farther to the right, whereas the weakly interacting SNPs are connected by keys farther to the left. (B) Interaction entropy graph. Each SNP are represented by a node and percentages inside the nodes are their entropy values. The percentages between the nodes indicate the entropy values resulting from the combination between SNPs.